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Chikungunya virus (CHIKV) is an arbovirus capable of causing a severe and often debilitating rheumatic syndrome in humans. CHIKV replicates in a wide variety of cell types in mammals, which has made attributing pathologic outcomes to replication at specific sites difficult. To assess the contribution of CHIKV replication in skeletal muscle cells to pathogenesis, we engineered a CHIKV strain exhibiting restricted replication in these cells via incorporation of target sequences for skeletal muscle cell-specific miR-206. This virus, which we term SKE, displayed diminished replication in skeletal muscle cells in a mouse model of CHIKV disease. Mice infected with SKE developed less severe disease signs, including diminished swelling in the inoculated foot and less necrosis and inflammation in the interosseous muscles. SKE infection was associated with diminished infiltration of T cells into the interosseous muscle as well as decreased production of Il1b, Il6, Ip10, and Tnfa transcripts. Importantly, blockade of the IL-6 receptor led to diminished swelling of a control CHIKV strain capable of replication in skeletal muscle, reducing swelling to levels observed in mice infected with SKE. These data implicate replication in skeletal muscle cells and release of IL-6 as important mediators of CHIKV disease., Introduction Viral cell and tissue tropism is an important determinant of viral pathogenesis. The capacity to replicate in a particular cell or tissue is often an essential precursor to the [...]

Chikungunya virus (CHIKV), a reemerging arbovirus, causes a crippling musculoskeletal inflammatory disease in humans characterized by fever, polyarthralgia, myalgia, rash, and headache. CHIKV is transmitted by Aedes species of mosquitoes and is capable of an epidemic, urban transmission cycle with high rates of infection. Since 2004, CHIKV has spread to new areas, causing disease on a global scale, and the potential for CHIKV epidemics remains high. Although CHIKV has caused millions of cases of disease and significant economic burden in affected areas, no licensed vaccines or antiviral therapies are available. In this Review, we describe CHIKV epidemiology, replication cycle, pathogenesis and host immune responses, and prospects for effective vaccines and highlight important questions for future research., Ecology and epidemiology Chikungunya virus (CHIKV) is a mosquito-borne virus responsible for periodic and explosive outbreaks of a febrile disease that is characterized by severe and sometimes prolonged polyarthritis. CHIKV [...]

The effect of adiabatic heating on microstructure evolution during high strain rate subtransus forging of a Ti-6Al-4V alloy having equiaxed initial microstructure was studied through experiments and modelling. Ø45 × 67.5 mm cylindrical billets with embedded thermocouples were forged at four different α+β temperatures on a Schuler 2100t screw press to evaluate the extent of adiabatic heating in different parts of the billet. In the centre of the billet, the highest temperature increase due to adiabatic heating exceeded the β transus (~1000 °C) during forging. The microstructure of the forged billets was examined for any changes in β phase volume fraction due to adiabatic heating. The forging process was then simulated in Deform 2D/3D software. High strain rate compression testing in the α+β and β temperature fields was carried out using a Phoenix forge simulator to generate input mechanical properties for the model. The effect of the billet size on the α-β phase transformation during forging and post-forge cooling is also discussed.

Background Chikungunya virus (CHIKV) is an arbovirus that periodically emerges to cause large epidemics of arthritic disease. Although the robust immunity elicited by live-attenuated virus (LAV) vaccine candidates makes them attractive, CHIKV vaccine development has been hampered by a high threshold for acceptable adverse events. Methods We evaluated the vaccine potential of a recently described LAV, skeletal muscle-restricted virus (SKE), that exhibits diminished replication in skeletal muscle due to insertion of target sequences for skeletal muscle-specific miR-206. We also evaluated whether these target sequences could augment safety of an LAV encoding a known attenuating mutation, E2 G82R. Attenuation of viruses containing these mutations was compared with a double mutant, SKE G82R. Results SKE was attenuated in both immunodeficient and immunocompetent mice and induced a robust neutralizing antibody response, indicating its vaccine potential. However, only SKE G82R elicited diminished swelling in immunocompetent mice at early time points postinoculation, indicating that these mutations synergistically enhance safety of the vaccine candidate. Conclusions These data suggest that restriction of LAV replication in skeletal muscle enhances tolerability of reactogenic vaccine candidates and may improve the rational design of CHIKV vaccines. [ABSTRACT FROM AUTHOR]

Chikungunya virus (CHIKV) is a mosquito-transmitted, RNA virus that causes an often-severe musculoskeletal illness characterized by fever, joint pain, and a range of debilitating symptoms. The virus has re-emerged as a global health threat in recent decades, spreading from its origin in Africa across Asia and the Americas, leading to widespread outbreaks impacting millions of people. Despite more than fifty years of research into the pathogenesis of CHIKV, there is still no curative treatment available. Current management of CHIKV infections primarily involves providing supportive care to alleviate symptoms and improve the patient’s quality of life. Given the ongoing threat of CHIKV, there is an urgent need to better understand its pathogenesis. This understanding is crucial for deciphering the mechanisms underlying the disease and for developing effective strategies for both prevention and management. This review aims to provide a comprehensive overview of CHIKV and its pathogenesis, shedding light on the complex interactions of viral genetics, host factors, immune responses, and vector-related factors. By exploring these intricate connections, the review seeks to contribute to the knowledge base surrounding CHIKV, offering insights that may ultimately lead to more effective prevention and management strategies for this re-emerging global health threat. [ABSTRACT FROM AUTHOR]

The processing of washed, minced mackerel muscle was made more effective when, in the early stages, an antioxidative system designed to maintain heme iron reduced, nonheme iron as an inactive chelate and provide free radical scavenging in the aqueous and lipid phases, was added. Dark muscle mackerel mince showed a geater propensity to oxidate than did the light muscle mince. There was no loss of odor quality for washed light muscle mince when in the presence of the antioxidative system, even though this meat was frozen at -20 degrees Centigrade for 23 weeks. The initial odor quality of the washed mince was not affected by the postmortem age of the mackerel muscle.

SYNCHRONIZED OSCILLATIONS ARE pervasive in the cerebral cortex. Cortical rhythms, as revealed by the electro-encephalogram (EEG), vary with behavioral state; their frequencies range from the 4- to 7-Hz theta waves [...]

Recent years have brought a rise in newly emergent viral infections, primarily in the form of previously known arthropod‐transmitted viruses that have increased significantly in both incidence and geographical range. Of particular note are DENV, CHIKV, and ZIKV, which are transmitted mostly by Aedes species of mosquitoes that exhibit a wide and increasing global distribution. Being important pathogens for the general population, these viruses have the potential to be devastating in the international transplant community, with graft rejection and death as possible outcomes of infection. In this review, we discuss the current state of knowledge for these viruses as well as repercussions of infection in the solid organ and HSCT population, with a focus, when possible, on pediatric patients. [ABSTRACT FROM AUTHOR]